The last decade of cardiac surgery has witnessed significant strides towards better understanding and better management of previously lethal cardiac pathology.
Myocardium (heart muscle) and other tissues of the human body can sustain structural metabolic and functional damage by prolonged ischemia, the loss of blood flow to the tissues caused by a blocked artery. The extent and severity of the damage depends on a number of factors including the nature of the ischemic event and the health of the tissue prior to the event. In extreme cases the ischemic event can result in necrotic or irreversibly damaged tissue. In other cases the ischemic event can leave the tissue stunned or hibernating. Although stunned and hibernating tissue closely resembles necrotic tissue, it is still viable and can be returned to a functional state by reperfusion, the return of blood flow caused by opening the artery.
Determinations of tissue viability are often used by cardiologists and surgeons as the basis for critical patient treatment decisions. High risk procedures, for example, will typically be performed only if the cardiologists and surgeons believe there is a sufficient quantity of viable tissue that the potential for successful outcomes outweigh the risks. Accurate assessments of tissue viability are therefore required to select appropriate interventional treatments.
It is evident that there is a continuing need for improved tissue viability monitoring instruments and methods. Timely and accurate information on tissue viability will enable cardiologists and surgeons to more reliably determine the most appropriate treatment programs for their patients. Improved patient health can therefore be obtained with reduced burdens on the health care system.
Two important manifestations stand out in particular. First, the decade has witnessed a remarkable improvement in techniques for preserving the myocardium (heart muscle) from irreversible damage, coupled with a widening choice of sophisticated ways to correct myocardial ischemia. Second, practitioners generally recognize new conditions such as myocardial stunning and hibernation where the injured myocardium is in a state of "suspended animation," closely resembling total necrosis but very different in practice since it retains enough viability to allow for function retrieval by modern techniques. Varying intermediate degrees of the above situations have also been identified.
Faced with the recognition of this widening variety of ischemic clinical pictures with variable degrees of retained viability, and armed with the knowledge that several conditions previously considered hopeless can now be salvaged if appropriately recognized as viable, cardiologists and cardiac surgeons are increasingly aware of the need to optimize selection from their ever-widening choice of techniques in a way that matches the particular clinical situation.
By necessity, such a goal would depend on our ability to assess viability in an injured myocardium as accurately as possible.
The regional nature of coronary occlusive disease produces a need for a non-invasive means of assessing regional oxidative metabolism in cardiac patients. To those familiar with this art, there is no method presently known of accurately and quickly measuring regional tissue oxygen availability and utilization in human beings. Standard clinical indicators are insensitive to the non-uniform drop-out of myocardial perfusion-metabolism units associated with coronary insufficiency. Radionuclide and angiographic methods permit the evaluation of myocardial perfusion and ventricular wall motion, but the metabolic state of the myocardium cannot be reliably predicted with these methods, particularly in patients with marginal perfusion and/or abnormal ventricular wall motion.
Known techniques for monitoring tissue viability include positron emission tomography (PET), nuclear magnetic resonance (NMR), thallium scans and ultrasound backscatter. Unfortunately, these techniques are relatively time consuming and expensive. They are also sometimes inaccurate. The use of these monitoring techniques can therefore result in prolonged or complicated patient treatment decisions, unnecessary and expensive tests, and incorrect diagnoses.
Current methods for assessing myocardial viability each have significant shortcomings. (1) The "educated clinical guess" is based on EKG readings and cardiac enzyme measurements, angiographic evidence of ventricular contractility and collateral circulation. This provides a sound general assessment but lacks the accuracy needed to fine-tune the clinical and surgical management. (2) Thallium 201 perfusion/redistribution studies are used to outline regions of cardiac ischemia or scarring. Unfortunately, these studies are time consuming, cannot be applied to acute conditions, and have been proved inaccurate in diagnosing scar in 32% of cases (as shown by PET scanning). (3) Position emission tomography (PET) scanning utilizes a radioactive metabolic tracer, usually a glucose analogue, to follow tracer uptake by viable myocardial cells, as detected by positron emission. This method is the most accurate detector of viable myocardium so far but it is complicated and quite expensive, and is not practical in the acute phase so it is only used in a few academic centers. (4) Biopsy specimens may show metabolic and structural signs of irreversible damage such as the adenosine triphosphate (ATP) intracellular levels and triphenyltetrazolium chloride (TTC) vital staining (or lack thereof). Although these tests were previously accepted as reliable, they have now been found to be inaccurate. R. J. Barnard, et al., "Studies of Controlled Reperfusion After Ischemia--III. Histochemical studies: Inability of triphenyltetrazolium chloride nonstaining to define tissue necrosis," J. Thorac. Cardiovasc. Surg. 92:502-12 (1986). For example, a recently necrotic cell or stunned myocardium will show similar low levels of ATP yet the stunned myocardium could be saved if recognized and treated promptly. Of the presently available methods, PET scanning comes closest to fulfilling the need for assessing viability. However, it is expensive, often impractical and still does not help in the acute phase.
Some methods of measuring myocardial metabolism such as Magnetic Resonance Imaging/Spectroscopy and Positron Emission Tomography are costly and require cumbersome equipment (magnets and cyclotrons) which are not compatible with the cardiac catheterization laboratory setting found in most hospitals and/or clinics. The test procedures also require considerable time to carry out, and a patient suffering an acute heart attack generally cannot be evaluated by these methods with enough time left to implement a corrective procedure.
The capacity to rapidly discern the metabolic state of the beating human heart, particularly within abnormally contracting myocardial segments, would beneficially affect clinical decisions regarding the need for therapeutic interventions such as blood clot dissolving agents, balloon angioplasty, and coronary artery bypass grafting.
Several researchers have worked on steady state evaluations using a variety of spectrophotometric methods. A good review of the prior art spectrophotometric methods for measuring circulatory and respiratory functions, arterial blood oxygenation and blood samples is set forth in U.S. Pat. Nos. 4,223,680 and 4,281,645 to Jobsis. The application of differential spectroscopy using near infrared (NIR) light in blood perfused body organs was advanced by Jobsis as described in detail in the aforementioned patents.
Jobsis emphasized in these patents that near infrared (NIR) light must span a relatively long path (e.g. several centimeters) in length in order for his invention to work. The long path length is significant in that it allows the light photons to travel deeply into the tissue of interest so that the received optical signal will contain information from a substantial volume of tissue. Also, the longer path length minimizes the light-scattering effects of structures which are superficial to the region of interest. Since, as shown in FIG. 2 of U.S. Pat. No. 4,223,680, the back-scattered light from superficial structures may not contain metabolic information of interest, and may obscure detection of the desired metabolic information, a method was sought by Jobsis to minimize this biophysical effect. Accordingly, both Jobsis patents teach that the near infrared (NIR) light must be transmitted to the test organ (in situ) and then the radiation intensity must be detected and measured at a point spaced apart from the point of light entry. As indicated in FIG. 1 and FIG. 2 of U.S. Pat. No. 4,223,680, the physical distance between entrance and exit of near infrared (NIR) light is specified to be several centimeters.
Others follow the Jobsis teaching that the light detector fiber bundle must be spaced apart from the light source fiber bundle to minimize light scattering from superficial tissue regions. Parsons et al., in U.S. Pat. No. 5,161,531 and 5,127,408 disclose bundles spaced apart even if the light source fiber bundle and light detector fiber bundle are oriented parallel to each other as suggested by Abe in U.S. Pat. No. 4,513,751. Simply transmitting near infrared (NIR) light down one optical fiber and receiving the reflected light with a second optical fiber which is parallel and immediately adjacent to the transmitting fiber, as proposed by Abe for visible light wavelengths, will not permit the desired accurate near infrared (NIR) measurement of oxidative metabolism within a substantial tissue volume.
Summarily, it is highly desirable for intravascular application of a red to near-infrared (NIR) light sending and receiving device that a single scope containing both the transmitting and receiving optical fibers be used to acquire optical information from an endocardial site. The introduction of two separate send and receive scopes by a percutaneous, intravascular approach to the endocardium would be hampered by motion artifact of the beating myocardial wall and the instability of the optical alignment of the two scopes relative to the tissue region of interest. Parsons et al. sought to overcome the shortcomings of the prior art as disclosed in the Jobsis and Abe patents by using a steerable fiber optic device to deliver and receive near infrared (NIR) light through a single small-diameter scope (less than 3.3 mm in diameter) positioned at the endocardial surface by means of a percutaneous intravascular approach which is applicable in a standard clinical catheterization laboratory. The procedure using the Parsons et al. device can be done as part of a routine diagnostic catheterization study, and permits the steady-state measurement of regional myocardial oxygenation from within the beating heart.
A variety of products and devices that enter the cardiac cavity and vascular lumen, and myocardium are currently used to evaluate tissue status.
______________________________________ Products Primary Users ______________________________________ Cardiac catheters Cardiologists Electrophysiology pacing wires Cardiologists, Surgeons Biopsy device Surgeons Hemo-pump Surgeons Intravascular ultrasound Cardiologists Atherectomy device/catheter Cardiologists Laser fibers Cardiologists Coronary angioscope Cardiologists ______________________________________
Many of these procedures are performed on a daily basis in most acute care centers with cardiac catheterization being the most frequent intervention. No valvular damage is caused by any of these devices as they cross the valves. Stenotic (narrowed) valves in certain diseases may not allow passage of the catheter. Prosthetic valves do not allow passage of the catheter.
Prospect For PET, NMR, and Ultrasound Backscatter Technology
Positron emission tomography (PET) has many limitations, many of which are anticipated to be insurmountable over the next 3-5 years. PET is a large expensive device. It is therefore rarely available even in large medical centers. Miniaturization of the technology and reduction of its cost is most unlikely over the next five years. A good example of this is Nuclear Magnetic Resonance (NMR) technology, also known as magnetic resonance imaging (MRI). NMR is a very old technology, originally developed over 40 years ago. To date, MRI imaging machines are very large, very expensive and only sometime available even in large medical centers. Similarly, computerized axial tomography machines (CT or CAT scanners), although more widely available now, are still very large, expensive and require specific building and structural arrangement. Many hospitals rely on leasing mobile scanners or simply refer studies to outside service providers. Each of these difficulties means the analytical equipment is relatively less available but only limited time is available for evaluating viable tissue after an ischemic attack. This time is optimally one to two hours, although useful recovery is possible in some cases after several hours.
In addition to these limitations, PET scanners cannot detect myocardial damage in the acute state of myocardial infarction. Furthermore, it is very unlikely to place a patient suffering an acute myocardial infarction inside a large scanner in the radiology department for a prolonged period of time while images are being collected. More appropriately, such a patient should be in the cardiac catheterization laboratory where the heart can be catheterized, myocardial wall viability assessed with the tissue viability monitor, and appropriate interventions performed.
A further series limitation of the PET scanner is the need for a facility to generate radioactive isotope. Such facilities are large, expensive, and not usually present in many large cities. The isotope half-life is very short. The remoteness of the isotope generating facility from most cities and medical centers and the short half-life of the isotope require the special ordering of the isotope acutely for each selected case and the use of airlines to deliver the short-lived isotope, a sequence that is expensive, cumbersome and rarely available to most medical centers. Such limitations will not change significantly over the next five years and beyond.
Backscatter Ultrasound Technology
Transthoracic ultrasound technology has been used to evaluate cardiac tissue conditions, including some attempts to identify hibernating versus dead myocardium. M. R. Milunski, et al., "Ultrasonic Tissue Characterization With Integrated Backscatter," Circulation, 80: 491-503 (1989). This technology is limited by the quality of the image. The ultrasound image is compromised by many factors including chest wall size, obesity and most importantly lung disease. A great majority of older patients have lung disease (e.g. chronic obstructive pulmonary disease or COPD) which significantly compromises the backscatter image quality. Many times these are the same patients who have cardiac problems as well and need evaluation. The present invention can be used in backscatter ultrasound evaluation to provide additional information about the physiological integrity of apparently dead tissue.
Without a clear transthoracic ultrasound image, current backscatter technology is somewhat limited. However, for some patients, backscatter may provide an alternative means for evaluating tissue viability. To overcome transthoracic poor image quality in many patients, echocardiography can be performed invasively by the transesophogeal approach. The Endosonics Oracle-Micro intra-arterial ultrasound imaging catheter recently approved by the FDA may be useful.